The primary goals of this research are i) to establish how learning impacts the structure and function of the brain, and ii) to determine how learning can be modulated by factors such as feedback (positive or negative). Over the past year we have focused equally on both of these goals. 1) Impact of learning on brain structure and function (NCT00001360) Over the past few years, we have been conducting a long-term longitudinal study of participants learning different tasks (e.g. motor sequences, spatial layout) to determine how structural properties of the brain (gray matter, white matter) change over time. Over a period of four weeks, participants were trained in two different tasks and we collected extensive functional and structural MRI data over the course of training. While previous studies have identified structural changes associated with learning, even over the course of a couple of hours, our initial findings have highlighted a potential confound that needs to be accounted for in such studies. Specifically, we have found that the structural and functional measures obtained with MRI fluctuate according to the time of day. Structurally, we observed decreases in cortical thickness and increases in ventricular volume as well as increases in free water volume fraction that is associated with an increase in cerebrospinal fluid. Functionally, we observed changes in resting state connectivity in the same regions where we saw structural changes. Collectively, these results suggest that the diurnal fluctuations in MRI measures that we detected have an underlying physiological basis and may reflect the impact of the circadian rhythm. Interestingly, these fluctuation appear to be modulated by training and we are trying to establish what additional structural and functional changes occur with training above and beyond these time-of-day effects. With the motor sequence task we find that, following training, sensorimotor networks show changes in their functional connectivity. In contrast, with the spatial layout task, hippocampal networks change. These findings suggest task-specific changes in particular networks underlie learning above and beyond any changes due to circadian fluctuations. 2) Impact of feedback on learning (NCT00001360) We are investigating the impact of feedback (positive, negative) on motor learning. Groups of participants were trained on one of two different motor tasks and either provided with positive, negative or neutral (uninformative) feedback. Training occurred in the MRI scanner and we measured fMRI activity before, during and after training. Behaviorally, we found that the impact of feedback is dependent on the task. While in a sequence learning task we find that punishment improves online performance, we observe the opposite effect in a purely motoric force-tracking task. In terms of brain activity, we found that reward and punishment differentially affected the functional connectivity of premotor cortex (PMC, a region known to be critical for learning of sequencing skills) in a task-specific manner. For a serial reaction time task (pushing a sequence of buttons in response to visual cues), training with reward increased PMC connectivity with cerebellum and striatum, while training with punishment increased PMC-medial temporal lobe connectivity. For a force tracking task (sqeezing a bar to control the movement of a cursor on the screen), training with control and reward increased PMC connectivity with parietal and temporal cortices after training, while training with punishment increased PMC connectivity with ventral striatum. These findings suggest that reward and punishment influence spontaneous brain activity after training, and that the regions implicated depend on the task learned. Establishing the nature, degree and consequences of plasticity in the adult cortex provides important insights into the potential for rehabilitative brain therapies following injury or dysfunction in the nervous system.